br Materials and methods br Results and discussion br

Materials and methods
Results and discussion
Conclusions Robust approaches for electronic transduction of molecular binding events are of significant interest for the development of innovative sensor technologies. We have engineered and demonstrated a range of long-chain alkanethiols incorporating oligothyleneglycol linkers that can address this challenge. Specifically, we have demonstrated self-assembled molecular monolayers consisting of mixed components of LCAT-OEG-MB and LCAT-OEG-NH2. The NH2 component acts as a chemoselective scaffold for the immobilization of a binding molecule local to the redox active MB while the OEG component inhibits non-specific binding, maintaining specificity of the assay. Specific molecular binding events can be detected directly and label-free by monitoring the change in peptide yy transport properties of MB due to the corresponding change in local electrochemical environment. Given the versatility of LCAT-OEG monolayers, in terms of linker lengths, choice of functional group, and ability to create mixed component monolayers of high quality, our electrochemical sensing approach could be extended for the detection of a range of clinically relevant analytes by local immobilization of specific and selective immuno-receptors, such as antibodies, aptamers and antibody-mimetics.
Conflict of interest
Acknowledgements This research was funded by the EU through the Marie Curie ITN CAPACITE project, Grant number 608014 (SJ and EK), the EPSRC, Grant EP/J010731/1 (SJ and RSB), the University of York through an Institutional Equipment award (SJ), the Biomedical and Health Research Centre of the University of Leeds (RSB) and a Henry Ellison PhD Studentship (JM).
Introduction Alzheimer’s disease (AD) is the most common neurodegenerative disease. It is characterized by progressive memory loss and cognitive decline, as well as breakdown of social skills and emotional instability, primarily among elderly adults [39]. The number of people with AD is currently estimated to be 26 million; this number is predicted to be more than 100 million worldwide by 2050 [29]. However, no treatments that arrest or reverse AD are available to date, and only a few medicines can retard or alleviate progression of the disease [7,13,36]. Moreover, clinical diagnosis of AD relies largely on documenting mental decline, and definitive confirmation of the disease can be obtained only by post mortem examination of brain tissues for the amyloid plaques and neurofibrillary tangles that are the hallmark histopathological features of AD [21]. Amyloid-β peptide (Aβ), a 39–43 amino acid peptide that is proteolytically cleaved from the membrane-bound amyloid precursor protein, is the major constituent of amyloid plaques and is the most suspicious factor responsible for the progression of AD [14]. Since Aβ biomarker abnormalities precede other neurodegenerative biomarker abnormalities before symptoms of overt dementia have appeared, Aβ in bodily fluids [e.g., cerebrospinal fluid (CSF), blood, and plasma] is considered a promising biomarker for the early diagnosis of AD [17,33]. Currently, clinical practice in AD diagnostics is based upon the detection of Aβ with a sandwich enzyme-linked immunosorbent assay (ELISA) [28,38]. Although sandwich ELISA is reliable and highly sensitive, it requires a laborious procedure and a relatively expensive enzyme-linked antibody for Aβ. It has been pointed out that such a procedure is not suitable for early diagnostics of AD [30]. Over the past decade, therefore, there have been several advances in the development of sensitive, quantitative, and rapid methods for the detection of Aβ, such as surface plasmon resonance [11,12,42,48], quartz crystal microbalance (QCM) [30,31,32], capillary electrophoresis [34], resonance light scattering [45], gold nanoparticle immunoassay [10,46], fluorescence [9], and electrochemistry [19,25,26]. Most of these methods, however, require expensive and complicated apparatus. In anticipation of the aging of society, there is a growing need for the development of detection methods suitable for the early diagnosis of AD.